β-arrestin 2-dependent activation of ERK1/2 is required for ADP-induced paxillin phosphorylation at Ser(83) and microglia chemotaxis.

Loading...
Thumbnail Image

Date

2012-09

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

72
views
54
downloads

Citation Stats

Abstract

Microglia play crucial roles in increased inflammation in the central nervous system upon brain injuries and diseases. Extracellular ADP has been reported to induce microglia chemotaxis and membrane ruffle formation through P2Y(12) receptor. In this study, we examined the role of ERK1/2 activation in ADP-induced microglia chemotaxis. ADP stimulation increases the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and paxillin phosphorylation at Tyr(31) and Ser(83) . Inhibition of ERK1/2 significantly inhibited paxillin phosphorylation at Ser(83) and the retraction of membrane ruffles, causing inefficient chemotaxis. Close examination of dynamics of focal adhesion (FA) formation with green fluorescent protein-paxillin revealed that the disassembly of FAs in U0126-treated cells was significantly impaired. Depletion of β-Arrestin 2 (β-Arr2) with short hairpin RNA markedly reduced the phosphorylation of ERK1/2 and Pax/Ser(83) , indicating that β-Arr2 is required for ERK1/2 activation upon ADP stimulation. A large fraction of phosphorylated ERK1/2 and β-Arr2 were translocated and co-localized at focal contacts in the newly forming lamellipodia. Examination of kinetics and rate constant of paxillin formation and disassembly revealed that the phosphorylation of paxillin at Tyr(31) by c-Src appears to be involved in adhesion formation upon ADP stimulation while Ser(83) required for adhesion disassembly.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1002/glia.22355

Publication Info

Lee, Sang-Hyun, Ryan Hollingsworth, Hyeok-Yil Kwon, Narae Lee and Chang Y Chung (2012). β-arrestin 2-dependent activation of ERK1/2 is required for ADP-induced paxillin phosphorylation at Ser(83) and microglia chemotaxis. Glia, 60(9). pp. 1366–1377. 10.1002/glia.22355 Retrieved from https://hdl.handle.net/10161/21065.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.


Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.